Genomic characterization of virulent, attenuated, and revertant passages of a North American porcine reproductive and respiratory syndrome virus strain

Pigs were exposed to three passages of the NADC-8 strain of porcine reproductive and respiratory syndrome virus (PRRSV) to investigate the relationship between genotypic and phenotypic properties. Differences were found in the virulence of the three passages called virulent, intermediate, and avirulent. Avirulent virus was derived by attenuation of virulent virus in cell culture and intermediate virus was derived by passage of avirulent virus in a pig. Nucleotide sequence differences between virulent and avirulent virus consisted of 50 nucleotide changes and a three-nucleotide deletion, and between avirulent and intermediate virus consisted of 8 nucleotide changes resulting in six amino acid changes. Three of these amino acid changes were direct reversions to virulent virus. Genetic changes, especially those seemingly associated with attenuation followed by some degree of reversion to virulence, in ORF1a, ORF1b, and ORF 6 regions of the genome may be involved in the control of PRRSV replication and virulence